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However, it is not clear whether and how mammalian hibernators are resistant to ischemia\u2010induced arrhythmias. The goal of this investigation was to determine the susceptibility of woodchucks\n                    <jats:italic>(Marmota monax)<\/jats:italic>\n                    to arrhythmias and their mechanisms after coronary artery occlusion at the same room temperature in both winter, the time for hibernation, and summer, when they do not hibernate. By monitoring telemetric electrocardiograms, we found significantly higher arrhythmia scores, calculated as the severity of arrhythmias, with incidence of ventricular tachycardia, ventricular fibrillation, and thus sudden cardiac death (SCD) in woodchucks in summer than they had in winter. The level of catalase expression in woodchuck hearts was significantly higher, whereas the level of oxidized Ca\n                    <jats:sup>2<\/jats:sup>\n                    +\/calmodulin\u2010dependent protein kinase II (CaMKII) was lower in winter than it was in summer. Ventricular myocytes isolated from woodchucks in winter were more resistant to H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010induced early afterdepolarizations (EADs) compared with myocytes isolated from woodchucks in summer. The EADs were eliminated by inhibiting CaMKII (with KN\u201093), L\u2010type Ca current (with nifedipine), or late Na\n                    <jats:sup>+<\/jats:sup>\n                    current (with ranolazine). In woodchucks, in the summer, the arrhythmia score was significantly reduced by overexpression of catalase\n                    <jats:italic>(via<\/jats:italic>\n                    adenoviral vectors) or the inhibition of CaMKII (with KN\u201093) in the heart. This study suggests that the heart of the mammalian hibernator is more resistant to ischemia\u2010induced arrhythmias and SCD in winter. Increased antioxidative capacity and reduced CaMKII activity may confer resistance in woodchuck hearts against EADs and arrhythmias during winter. The profound protection conferred by catalase overexpression or CaMKII inhibition in this novel natural animal model may provide insights into clinical directions for therapy of arrhythmias.\u2014Zhao, Z., Kudej, R. K., Wen, H., Fefelova, N., Yan, L., Vatner, D. E., Vatner, S. F., Xie, L.\u2010H. Antioxidant defense and protection against cardiac arrhythmias: lessons from a mammalian hibernator (the woodchuck).\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 32, 4229\u2010240 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201701516r","type":"journal-article","created":{"date-parts":[[2018,2,28]],"date-time":"2018-02-28T17:46:48Z","timestamp":1519840008000},"page":"4229-4240","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Antioxidant defense and protection against cardiac arrhythmias: lessons from a mammalian hibernator (the woodchuck)"],"prefix":"10.1096","volume":"32","author":[{"given":"Zhenghang","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Medicine Xi'an Jiaotong University Xi'an China"},{"name":"Department of Cell Biology and Molecular Medicine Rutgers\u2010New Jersey Medical School Newark New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond K.","family":"Kudej","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine Rutgers\u2010New Jersey Medical School Newark New Jersey USA"},{"name":"Department of Clinical Sciences Tufts University North Grafton Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hairuo","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine Rutgers\u2010New Jersey Medical School Newark New Jersey USA"},{"name":"National Center for Safety Evaluation of Drugs National Institutes for Food and Drug Control Key Laboratory of Beijing for Nonclinical Safety Evaluation Research of Drugs Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadezhda","family":"Fefelova","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine Rutgers\u2010New Jersey Medical School Newark New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Rutgers\u2010New Jersey Medical School Newark New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy E.","family":"Vatner","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine Rutgers\u2010New Jersey Medical School Newark New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen F.","family":"Vatner","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine Rutgers\u2010New Jersey Medical School Newark New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai\u2010Hua","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine Rutgers\u2010New Jersey Medical School Newark New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,2,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.96.9.3215"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00008.2003"},{"key":"e_1_2_8_4_1","first-page":"826","article-title":"The hibernator heart\u2014nature's model of resistance to ventricular fibrillation","volume":"31","author":"Johansson B. 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